PB2433: APPLICATION GENE VARIATION DETECTION BEFORE AND AFTER HEMATOPOIETIC STEM CELL TRANSPLANTATION TO PREDICT THE RELAPSE OF PATIENTS AFTER TRANSPLANTATION: RETROSPECTIVE DATA FROM A SINGLE CENTER IN CHINA
Authors: Jia Liu, Yanqi Zhang, Peiyan Kong, Lidan Zhu, Shichun Gao, Lu Wang, Huanfeng Liu, Ting Chen, Yimei Feng, Han Yao, Yuqing Liu, Lu Zhao, Lei Gao, XI Zhang
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: Relapse is still the main cause of death for hematological neoplasm patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Effective prediction of relapse risk after transplantation can help clinicians judge whether to give intervention measures and what kind of intervention measures to give. Second-generation sequencing (NGS) technology has been widely used in the risk stratification and prognosis judgment of hematological neoplasms. Whether the gene variation detected with NGS after transplantation can predict the recurrence after transplantation is worthy of further study. Aims: To evaluate the changes of gene variation in patients with hematological neoplasms at the time of diagnosis and after allo-HSCT, and the relationship between gene mutation and recurrence after transplantation. Methods: 76 patients with hematological neoplasms were analyzed retrospectively, including 55 AML, 16 ALL, 4 MDS, 1 MAL and 1 CML. The median age was 35 years, with 42 males and 34 females. Among 76 patients, 13 were MDS-HSCT, 12 were MUS-HSCT, and 51 were haplo-HSCT. All patients underwent NGS of hematological neoplasms variation genes at the time of diagnosis and 28 days after transplantation. Results: Primary and Secondary variations were detected in 70 of 76 patients during diagnosis. Common variations include CEBPA (14/76), NRAS (10/76), FLT3 (8/76), DNMT3A (8/76), TP53 (6/76), etc. After transplantation, only 25 patients had variations, including ABCB1 (27/76), CYP2C19 (10/76). The above NGS detection results suggest that the number of primary and Secondary variations after transplantation is significantly reduced (p=0.019), and ABCB1 (27/76) and CYP2C19 are the main variation forms. SNP variations were detected in 42 of 76 patients at diagnosis, and GATA2 (20/76) and TET2 (21/76) variations were the most common variation forms. SNP variations of GATA2 and TET2 increased significantly after transplantation, 48/76 and 52/76 respectively. The increase of GATA2/TET2 double variation was more significant after transplantation (15/76 vs. 41/76, P<0.001). The increased variation frequency of GATA2 and TET2 after transplantation may be related to the mixed chimerism at the early stage of transplantation, which needs to be observed for a long time. Eight of 76 patients recurred after transplantation. The single factor competitive risk model showed that the presence of primary and Secondary variations after transplantation was an independent risk factor for recurrence (P=0.017) (Figure 1). Among them, the variation of TET2 gene has a good predictive effect on the recurrence after transplantation (P<0.001). The primary and secondary variations before transplantation, SNP variations before and after transplantation had no effect on recurrence after transplantation. The schemes of transplantation in 25 patients with primary and secondary variations after transplantation were analyzed, including 9 cases of MSD-HSCT, 11 cases of haplo-HSCT, and 5 cases of MUD-HSCT. It suggests that relative donors are more likely to have primary and secondary variations related to diseases. We used Fisher’s Exact Test to analyze the relationship between ASXL1, TP53, GATA2, RUNX1 and other high-risk variations at the time of diagnosis/after transplantation and recurrence, and did not find that the presence of these gene variations would increase the risk of recurrence after transplantation. Summary/Conclusion: The NGS gene variation detection before and after transplantation can predict the recurrence after transplantation. Large samples and long-term monitoring are also needed to find a more accurate variation pattern to predict the recurrence of hematological neoplasms after transplantation.Keywords: HSCT